Clear lens extraction (CLE) demonstrated improved efficacy over peripheral laser iridotomy (laser PI), with a significant reduction in topical medications or surgical treatment 36 months postoperatively, and was more cost effective, according to the results of the Effectiveness of Early Lens Extraction for the Treatment of Primary Angle-Closure Glaucoma (EAGLE) trial,1 which compared the outcomes between these two procedures in newly diagnosed primary angle closure (PAC) patients. According to Gordana Sunaric-Megevand, MD, Geneva, Switzerland, ophthalmologists need to exercise caution interpreting results.
“The EAGLE study is a well-designed study, but we need to remind ourselves that the main differences were based on the patient-perceived outcomes, which were visual acuity and the continued use of medications,” Dr. Sunaric-Megevand said. “These data may be insufficient to be generalized to all PAC/PACG eyes. However, we can imagine using this approach in countries with high PAC/G prevalence, such as Asia, or in areas with low resources.”
The EAGLE study included 419 individuals—155 with primary angle closure and 263 with primary angle closure glaucoma (in one patient the diagnosis was unknown)—enrolled from 30 hospitals in five countries. The patients were randomized by web-based application to receive either CLE (n=208) or standard care with laser PI and topical medication (n=211). They were more than 50 years old, without cataract, and had either newly diagnosed PAC with IOP 30 mm Hg or higher or PACG. Patients with advanced, symptomatic cataract were excluded, as well as individuals with glaucoma (MD<–15 dB or C/D>0.9) or those who had experienced a previous acute angle closure attack, had previous laser or ocular surgery, or any increased surgical risk.

Primary and secondary endpoints

Primary endpoints of the EAGLE study included the European QoL-5 Dimensions questionnaire (EQ–5D) score for health-related questions, IOP, and cost-effectiveness. CLE exceeded peripheral LI for all primary endpoints. The mean health status score (QoL-5 questionnaire score) was significantly better after clear lens extraction than after peripheral laser at 36 months. The difference in change between the two groups from baseline to 36 months was 0.052 (95% CI 0.015–0.088; p=.005).
IOP outcomes in clear lens eyes were lower (16.6 mm Hg ± 3.5 mm Hg) than that achieved in the laser PI group. The difference between the two groups after the 3-year follow-up time period was significant but not large, at –1.18 mm Hg in favor of CLE (95% CI –1.99 to –0.38; p=.004).
“One of the major mechanisms of PAC or PACG is the age-related growth of the lens, and therefore, it is not surprising that IOP has been successfully lowered in our glaucoma patients following cataract surgery with lens extraction,” Dr. Sunaric-Megevand said. “Several studies have shown that cataract surgery by itself may lower IOP.”
Cost-effectiveness results were also better in CLE eyes compared to standard care eyes and likely to improve with longer follow up, according to the study authors. The incremental cost-effectiveness ratio was GBP 14,284 per QALY gained for CLE versus laser PI.
In terms of secondary endpoints, the application of topical medication was much lower after lens extraction than after laser: 0.4 ± 0.8 medications in the CLE group compared to 1.3 ± 1.0 medications in the laser group. This reflected a 21% use of topical drops in CLE eyes compared to 61% in laser PI eyes.
PACG, if uncontrolled with medication, needs trabeculectomy, which can have serious complications. Trabeculectomy was performed postoperatively in one of the CLE eyes and in six of the lasered eyes. Visual fields were similar between the two groups, with 24 CLE patients and 30 laser PI patients showing worse visual field results by the end of the study.

Study limitations

“CLE is superior to laser PI for PAC and PACG and should be considered as an option for first-line treatment, according to the study authors. The study, however, has certain strengths and limitations,” Dr. Sunaric-Megevand said. “While EAGLE has the strength of being a multicenter trial with a pragmatic, prospective, longitudinal study design that considers QoL, which is not often a primary outcome measure, along with a large sample size and strictly applied protocols, it has limitations, such as potential sampling bias. During recruitment, 48% of patients were excluded, while others did not choose to participate because they did not want CLE but preferred laser. Furthermore, QoL is based on patient perception not on the real state of AC/ACG. The study excluded severe PACG patients and included PAC only if the IOP was greater than or equal to 30 mm Hg, which represents the minority of patients within this group,” she said.
It is noteworthy that all of the surgeons involved in the EAGLE study were highly specialized, Dr. Sunaric-Megevand said. Intraoperative complications in the CLE group included: two posterior capsule ruptures, two iris prolapses, one case of vitreous loss, and one broken haptic. In the laser PI group, there were 16 cases of bleeding. Postoperatively, the surgeons experienced: flat anterior chamber in the CLE group (n=2) and laser group (n=1); malignant glaucoma after CLE (n=1) and laser PI (n=2); macular edema in CLE (n=5) and laser (n=3); IOP spikes after CLE (n=2) and laser (n=5); and postoperative inflammation in the CLE group (n=5) and in the laser group (n=1).
“One major limitation is that CLE in angle closure is technically challenging due to short axial lengths in these eyes, shallow AC, and low endothelial cell count. We could imagine potentially severe complications in the hands of less experienced surgeons than those involved in the study, such as PC rupture, endophthalmitis, endothelial cell loss, macular edema, and malignant glaucoma. PC rupture and endophthalmitis are decreasing over time thanks to our better techniques and use of antibiotics. But
in this group of challenging cases, it can be a concern,” Dr. Sunaric-Megevand said.
Other study limitations include the definitions used for PAC and PACG and the fact that the study did not look at subtypes. “Plateau iris was not considered and we know that lens extraction does not always resolve the problem in these cases. Also, gonioscopy data were lacking, with the degrees of appositional and synechial angle closure not reported in most participants,” she noted.
“This excellent study has shown that clear lens extraction has better efficacy and cost-effectiveness than laser PI in PAC and PACG eyes. More randomized studies are needed that include other subtypes of AC/ACG and for other states of the disease. I would recommend CLE for PAC/PACG after weighing the risk/benefit in your own environment and according to your own skills and the patient’s individual needs,” Dr. Sunaric-Megevand said.